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1.
Water Sci Technol ; 80(3): 551-562, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31596266

RESUMO

Exposure to antibiotics, biocides, chemical preservatives, and heavy metals in different settings such as wastewater treatment plants (WWTPs) may apply selective pressure resulting in the enrichment of multiple resistant, co- and cross-resistant strains of bacteria. The purpose of this study was to identify and characterize potentially pathogenic triclosan (TCS) - and/or, chloroxylenol (PCMX) tolerant bacteria from sewage and river water in the North-West, Potchefstroom, South Africa. Several potential pathogens were identified, with Aeromonas isolates being most abundant. Clonal relationships between Aeromonas isolates found at various sampling points were elucidated using ERIC-PCR. Selected isolates were characterized for their minimum inhibitory concentrations against the biocides, as well as antibiotic resistance profiles, followed by an evaluation of synergistic and antagonistic interactions between various antimicrobials. Isolates were also screened for the presence of extracellular enzymes associated with virulence. High-performance liquid chromatography revealed the presence of both biocides in the wastewater, but fingerprinting methods did not reveal whether the WWTP is the source from which these organisms enter the environment. Isolates exhibited various levels of resistance to antimicrobials as well as several occurrences of synergy and antagonisms between the biocides and select antibiotics. Several isolates had a very high potential for virulence but further study is required to identify the specific virulence and resistance genes associated with the isolates in question.


Assuntos
Desinfetantes , Eliminação de Resíduos Líquidos , Águas Residuárias/microbiologia , Antibacterianos , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Rios , Esgotos , África do Sul
2.
Rev Soc Bras Med Trop ; 52: e20190237, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31508785

RESUMO

INTRODUCTION: The increased use of colistin against infections caused by Acinetobacter baumannii and Pseudomonas aeruginosa has resulted in colistin resistance. The purpose of this study was to detect plasmid-mediated mcr-1 gene in colistin-resistant A. baumannii and P. aeruginosa isolates. METHODS: A total of 146 clinical isolates of A. baumannii (n = 62) and P. aeruginosa (n = 84) were collected from the four largest tertiary care hospitals in Peshawar, Pakistan. All bacterial isolates were phenotypically screened for multidrug resistance using the Kirby-Baur disc diffusion method. The minimum inhibitory concentration (MIC) of colistin in all isolates was phenotypically performed using dilution methods. mcr-1 gene was detected through polymerase chain reaction and the nucleotide sequence of amplicon was determined using Sanger sequencing. RESULTS: Approximately 96.7% A. baumannii and 83.3% P. aeruginosa isolates were resistant to multiple antibiotics. Colistin resistance was found in 9.6% (6/62) of A. baumannii and 11.9% (10/84) of P. aeruginosa isolates. Among 16 colistin resistant isolates, the mcr-1 gene was detected in one A. baumannii (1.61% of total isolates; 16.6% of colistin resistant isolates) and one P. aeruginosa strain (1.19% of total isolates; 10% of colistin resistant isolates). Nucleotide BLAST showed 98-99% sequence similarity to sequences of the mcr-1 gene in GenBank. CONCLUSIONS: Our study reports, for the first time, the emergence of plasmid-mediated mcr-1-encoded colistin resistance in multidrug resistant strains of A. baumannii and P. aeruginosa. Further large scales studies are recommended to investigate the prevalence of this mode of resistance in these highly pathogenic bacteria.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Proteínas de Bactérias/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Acinetobacter baumannii/efeitos dos fármacos , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Paquistão , Plasmídeos/genética , Pseudomonas aeruginosa/efeitos dos fármacos
3.
Rev Soc Bras Med Trop ; 52: e20190243, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31508786

RESUMO

INTRODUCTION: In recent decades, the prevalence of carbapenem-resistant Acinetobacter isolates has increased, and the production of oxacillinase (OXA)-type carbapenemases is the main mechanism underlying resistance. We evaluated OXA production from 114 Acinetobacter isolates collected between March and December 2013 from different clinical specimens of patients in two hospitals (Hospital 1 [n = 61] and Hospital 2 [n = 53]) located in Niterói, Rio de Janeiro, Brazil. We also evaluated the genetic diversity of OXA-producing isolates. METHODS: All the isolates were identified through the automated system Vitek II and matrix-assisted laser desorption ionization-time of flight mass spectrometry MALDI-TOF MS as belonging to the A. baumannii-A. calcoaceticuscomplex. Antimicrobial susceptibility profiles were verified through agar diffusion tests. The presence of OXA-encoding genes was confirmed by PCR. The genetic diversity of isolates positive for carbapenemase production was analyzed through pulsed-field gel electrophoresis. RESULTS: There was a high rate of resistance to carbapenems in the isolates (imipenem: 96%; meropenem: 92%) from both hospitals. Moreover, a high percentage (95.6%) of OXA-23-positive isolates was observed for both hospitals, indicating that this was the main mechanism of carbapenem-resistance among the studied population. In addition, most isolates (96.5%) were positive for bla OXA-51. A high genetic diversity and a few major genotypes were found among the OXA-23-positive isolates analyzed. Only intra-hospital dissemination was observed. CONCLUSIONS: The elevated dissemination of bla OXA-23-like observed among Acinetobacter isolates from both the studied hospitals highlights the need for continuous epidemiological surveillance in these institutions.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter/enzimologia , beta-Lactamases/biossíntese , Acinetobacter/efeitos dos fármacos , Acinetobacter/genética , Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana , Brasil , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Hospitais Gerais , Humanos , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , beta-Lactamases/efeitos dos fármacos
4.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(8): 900-903, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31484251

RESUMO

Objective: To understand the epidemiological characteristics and antibiotic resistance profiles of Campylobacter spp. in Shanghai from 2013 to 2016. Methods: Stool samples collected from diarrhea outpatients were cultured for Campylobacter spp., using the membrane filter method in 23 hospitals under the sentinel programs, from 2013 to 2016. All the strains were identified by biochemical tests and PCR. Broth microdilution method was used to investigate the antibiotic resistance of 179 Campylobacter spp. strains that including azithromycin, ciprofloxacin, erythromycin, gentamicin, tetracycline, nalidixic acid, telycin, klinthromycin and flurbenicol. Results: A total of 179 Campylobacter spp. strains were isolated from 10 444 stool samples (1.7%). Campylobacter jejuni and Campylobacter coli appeared as the predominant ones (94.4% and 5.6%). The incidence rate was higher in children than that in adults, with peaks of infections mainly from April to June and October to December. Campylobacter jejuni strains seemed highly resistant to ciprofloxacin (96.4%), tetracycline (83.4%) and nalidixic acid (81.7%). The resistant rates appeared higher on Campylobacter coli strains that isolated from patients. Some strains were resistant to multi-drugs. Conclusions: Campylobacter spp. seemed one of the important pathogens that isolated from outpatients with diarrhea, in Shanghai. Both age and season related characteristics of Campylobacter spp. were seen. Campylobacter spp. isolated from patients was highly resistant to ciprofloxacin, tetracycline and nalidixic acid.


Assuntos
Antibacterianos/farmacologia , Infecções por Campylobacter/tratamento farmacológico , Infecções por Campylobacter/epidemiologia , Campylobacter/efeitos dos fármacos , Campylobacter/isolamento & purificação , Diarreia/microbiologia , Fezes/microbiologia , Adolescente , Adulto , Distribuição por Idade , Antibacterianos/uso terapêutico , Campylobacter/classificação , Infecções por Campylobacter/diagnóstico , Infecções por Campylobacter/microbiologia , Campylobacter coli/efeitos dos fármacos , Campylobacter coli/isolamento & purificação , Criança , Pré-Escolar , China/epidemiologia , Diarreia/epidemiologia , Farmacorresistência Bacteriana , Humanos , Incidência , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Vigilância da População
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(8): 988-991, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31484266

RESUMO

Objective: To investigate the etiologic and epidemiologic features of an infectious diarrhea outbreak in a boarding school in Fuyang city, Anhui province. Methods: Traceability hypothesis of this study was tested according to the epidemiological characteristics of the cases. Feces, anal swabs, water samples and food residues related to the patients and chefs were collected for pathogen isolation and detection. Biochemical identification, virulence gene detection, drug susceptibility test, PFGE and multilocus sequence typing were performed. Results: The incidence rate (3.41%) of different dormitory buildings within the water supply area by shallow wells was higher than that (0.98%) of the deep wells, with statistical significance (χ(2)=17.215, P<0.001). Sixteen strains belonged to the Shigella Sonneri family were isolated from the patient's samples, and all carrying the ipaH gene. Seven strains belonged to sen and ial genes. Set1 gene that did not appear in all the 16 strains were highly resistant to ampicillin, tetracycline, compound xinnomine, cefazoline, cefotaxime, gentamicin, naphthidinic acid and streptomycin, including 9 strains to doxycycline. The pulse field pattern of the 16 strains of Shigella sonneri appeared the same, with the ST type as ST152. Conclusion: When combined data from the etiological and epidemiological investigation, it was confirmed that Shigella sonneri was the pathogen of this outbreak, and water from the shallow wells might be responsible for the source of infection.


Assuntos
Surtos de Doenças , Disenteria Bacilar/diagnóstico , Disenteria Bacilar/epidemiologia , Fezes/microbiologia , Adolescente , Antibacterianos/uso terapêutico , China/epidemiologia , Disenteria Bacilar/tratamento farmacológico , Disenteria Bacilar/microbiologia , Feminino , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Shigella sonnei/efeitos dos fármacos , Shigella sonnei/isolamento & purificação
6.
J Assoc Physicians India ; 67(8): 79-82, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31562727

RESUMO

Gross electrolytes disturbances including hypokalemia, hypomagnesaemia, and hypocalcaemia have been reported in tuberculosis patients who have been treated with capreomycin.1-3 Capreomycin is recommended in the treatment of M. tuberculosis isolates resistant to kanamycin at baseline in multi drug resistant tuberculosis patients (MDR - TB) and treatment of extensively drug resistant tuberculosis (XDR-TB) under programmatic management of drug resistant tuberculosis (PMDT) in India.4 We report a case of tetany in a extensively drug resistant tuberculosis (XDR-TB) patient treated with capreomycin. She developed hypokalemia after 7 weeks of administration of injection capreomycin intramuscularly daily in dose of 750 mg. Hypokalemia was refractory to intravenous potassium replacement therapy. At 12 weeks during the treatment she developed tetany and hypocalcaemia. Hypomagnesaemia was also associated with hypocalcaemia and hypokalemia. Normal level of serum potassium and calcium were achieved with correction of hypomagnesaemia.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Capreomicina/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos , Mycobacterium tuberculosis , Tetania/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos , Feminino , Humanos , Índia , Testes de Sensibilidade Microbiana
7.
J Assoc Physicians India ; 67(7): 93-97, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31559785

RESUMO

Antibiotic resistance is one of the biggest menace to global health. Deaths from Drug-resistant infections is set to escalate exponentially. Pipeline for new antibacterials is almost empty. The World Health Organization has reinforced its warning that to tackle growing threat of antimicrobial resistance, development of a new antibiotics is seriously lacking. Arbekacin is a novel aminoglycoside primarily used in the treatment of infections caused by resistant Staphylococcus Aureus i.e. Methicillin Resistant Staphylococcus Aureus (MRSA). Besides MRSA it also demonstrates activity against Enterococci and several Gram negative pathogens such as Klebsiella pneumonia, Pseudomonas aeruginosa, Acinetobacter baumannii including resistant strain. Arbekacin which has been used in Japan and Korea since more than two and half decades has been recently approved in India. This review will examine how Arbekacin evades the common mechanisms of antibiotic resistance, the pharmacokinetics of Arbekacin, and the various pharmacological properties and its spectrum of in vitro activity. The results of clinical trials on Arbekacin are also described, as is the patient safety and tolerability observed during these studies.


Assuntos
Antibacterianos/uso terapêutico , Dibecacina/análogos & derivados , Staphylococcus aureus Resistente à Meticilina , Dibecacina/uso terapêutico , Farmacorresistência Bacteriana , Humanos , Índia , Japão , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas
8.
J Agric Food Chem ; 67(38): 10646-10652, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31479255

RESUMO

A new monosesquiterpene diacetylgliocladic acid (1), a new dimeric sesquiterpene divirensol H (9), and two exceptionally novel trimeric sesquiterpene trivirensols A and B (11 and 12), together with another eight known congeners, were purified from an endophytic fungus Trichoderma virens FY06, derived from Litchi chinensis Sonn. whose fruit is a delicious and popular food. All of them were identified by comprehensive spectroscopic analysis, combined with biosynthetic considerations. Trivirensols A and B are unprecedented trimers of which three subunits are connected by two ester bonds of the sesquiterpene class. Relative to the positive control triadimefon, all the tested metabolites showed strong inhibitory activities against at least one phytopathogenic fungus among Penicillium italicum, Fusarium oxysporum, Fusarium graminearum, Colletotrichum musae, and Colletotrictum gloeosporioides. Notably, as metabolites of the endophytic fungus from L. chinensis, they all presented strong antifungal activities against C. gloeosporioides which causes anthracnose in L. chinensis.


Assuntos
Fungicidas Industriais/farmacologia , Litchi/microbiologia , Sesquiterpenos/farmacologia , Trichoderma/química , Colletotrichum/efeitos dos fármacos , Colletotrichum/crescimento & desenvolvimento , Endófitos/química , Endófitos/genética , Endófitos/isolamento & purificação , Endófitos/metabolismo , Frutas/microbiologia , Fungicidas Industriais/química , Fungicidas Industriais/metabolismo , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Doenças das Plantas/microbiologia , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Trichoderma/genética , Trichoderma/isolamento & purificação
9.
Pan Afr Med J ; 33: 146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31558943

RESUMO

Introduction: Infection due to multidrug-resistant microorganisms is a growing threat in healthcare settings. Acinetobacter species specifically A. baumannii is increasingly becoming resistant to most antimicrobial agents recommended for treatment. This study aimed to determine the antimicrobial susceptibility pattern of Acinetobacter species isolated from patients in Kenyatta National Hospital. Methods: We conducted a retrospective study based on VITEK 2 (BioMérieux) electronic records capturing identification and antimicrobial susceptibility of Acinetobacter isolates from patient samples analyzed between 2013 and 2015 at Kenyatta National Hospital microbiology laboratory. Generated data were analyzed using WHONET and SPSS. Results: A total of 590 Acinetobacter isolates were analyzed. 85% of the isolates tested were multi-drug resistant (MDR). Among the 590 isolates, 273 (46%) were from tracheal aspirates and 285 (48%) from the critical care unit. A. baumannii was the most frequently isolated species with high susceptibility to amikacin (77%) and poor susceptibility to ciprofloxacin (69-76%), tobramycin (37%) and meropenem (27%). Both A. lwoffii and A. haemolyticus had high susceptibility to amikacin (80-100%) and meropenem (75-100%). Conclusion: A. baumannii is resistant to commonly administered antibiotics. There is need for continuous antimicrobial resistance surveillance especially in health care facilities and strengthening of antibiotic stewardship programmes which will contribute to enhancement of infection control policies.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter/efeitos dos fármacos , Antibacterianos/farmacologia , Acinetobacter/isolamento & purificação , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Farmacorresistência Bacteriana Múltipla , Feminino , Hospitais , Humanos , Quênia , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
10.
Ann Agric Environ Med ; 26(3): 405-408, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31559794

RESUMO

INTRODUCTION: Carbapenemase-producing Enterobacteriaceae have spread rapidly through the countries and continents to become a global concern. One of the main reservoirs of NDM-1 positive strains from the Enterobacteriaceae family is the Indian subcontinent (Bangladesh, Pakistan, India). MATERIAL AND METHODS: During June 2017 - June 2018, rectal swab samples were collected routinely in all patients returning to Poland from South and South-East Asia. During molecular examinations gene blaNDM-1 encoding NDM-1 carbapenemase was detected. RESULTS: 31 patients were examined after returning to Poland from a trip to South and South-East Asia. The presence of New Delhi Metallo-ß-lactamase-1 producing Escherichia coli and Klebsiella pneumoniae was confirmed in three patients (9.7%) returning to Poland from travels to India. All the positive patients were hospitalized during the trip in a New Delhi hospital. CONCLUSIONS: Digestive tract carriage of NDM in a group of Polish travelers is a significant health and epidemiological problem. The study confirms the necessity for screening for carbapenemase-producing Enterobacteriaceae (CPE), particularly among travellers. Rectal swabs should be collected in every case of patients returning from international trips, and the possibility of environment-associated infections should be emphasized.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli/enzimologia , Klebsiella pneumoniae/enzimologia , Viagem , beta-Lactamases/metabolismo , Adulto , Proteínas de Bactérias/genética , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Feminino , Humanos , Índia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Masculino , Testes de Sensibilidade Microbiana , Polônia , beta-Lactamases/genética
11.
J Assoc Physicians India ; 67(9): 42-45, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31561688

RESUMO

Introduction: The incidence of the urinary tract infections caused by Candida species, are becoming more common. Recently, an increase in the incidence of infection caused by fungi especially non albicans candida species (NAC) has been reported. Several virulence factors like biofilm formation, toxin production and presence of adhesins contribute to its pathogenesis. Objectives: This study was undertaken to determine species distribution, biofilm formation and in-vitro antifungal susceptibility of candida isolated in our tertiary care hospital. Method: Eighty seven clinical isolates obtained from urine specimens were subjected to wet mount, Gram's stain and cultured on Sabouraud's Dextrose agar (SDA) medium. Conventional method for yeast identification was done. Biofilm forming ability of each isolate was detected using microtitre plate method. Antifungal susceptibility against posaconazole, amphotericin-B, fluconazole, itraconazole, ketoconazole, 5-flucytosine, voriconazole, and caspofungin was tested using Sensititre® Yeastone® (Trek diagnostic systems). Results and Discussion: Out of 87 candida isolates, 31.03% (n=27) were C. albicans and 68.97% (n=60) were non albicans candida species (NAC). Among 60 NAC, C. kruseii 29.89% (n=26), C. glabrata 24.14% (n=21), C. tropicalis 14.94% (n=13). Among all isolates, 36.78% (n=32) were biofilm producers and biofilm positivity more among C. albicans 55.56% (n=15) as compared to NAC 28.33% (n=17) (Pvalue<0.002). The maximum positivity was observed with isolates from plastic devices (61.8%). The minimum inhibitory concentrations of all antifungal drugs against all isolates were within susceptible range except for fluconazole which was resistant to C. kruseii. Conclusion: C. albicans remains the major isolate from urine samples and also biofilm formation as a virulence factor might have a higher significance for C. albicans than for NAC and its ability to form biofilm is intricately linked with ability of organisms to adhere, colonize and subsequently cause infection.


Assuntos
Antifúngicos/uso terapêutico , Biofilmes/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Antifúngicos/farmacologia , Candida/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária , Infecções Urinárias/microbiologia
12.
Klin Lab Diagn ; 64(8): 497-502, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31479607

RESUMO

The growing prevalence of metallo-ß-lactamase (MBL)-producing Pseudomonas aeruginosa in nosocomial pathogen populations has been attributed to their clonal spread, and/or horizontal transfer of MBL determinants in mobile genetic elements, including integrons. To characterize the genetic background of the beta-lactamase VIM-2 encoding gene in the population of carbapenemresistant (Carba-R) P. aeruginosa clinical isolates.The detection of class 1 integrons was performed by PCR. Typing of the class 1 integrons containing the blaVIM gene cassette was performed by the PCR-restriction fragment length polymorphism (RFLP) approach followed by sequencing of variable regions of class 1 integrons. Five types of the blaVIM-2-carrying integrons were identified: ST654-isolates accounting for more than 50% of the Carba-R population harbored In56; ST235-isolates contained In559 (26% Carba-R isolates); ST111-isolates (19% Carba-R isolates) were characterized by carrying In59-like integron; two ST235-isolates harbored In59 and In249 each. Except In56, carrying the only blaVIM-2-gene cassette, all other identified integron types harbored the genes of resistance to trimethoprim and/or aminoglycosides. No new types of integrons were identified in the P. aeruginosa clinical isolates. The observed correlation of the integron type with specific STs indicates a clonal dissemination of significant resistance determinant producers - ST111, ST654 and ST235 epidemic lines. The features of the integron variable regions can be used for the epidemiological characterization of clinical P. aeruginosa isolates.


Assuntos
Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Integrons , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , beta-Lactamases/genética , Antibacterianos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos
13.
Pan Afr Med J ; 33: 111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489089

RESUMO

Introduction: High mortality among individuals receiving retreatment for tuberculosis (RT-TB) persists, although reasons for these poor outcomes remain unclear. Methods: We retrospectively reviewed 394 RT-TB patients diagnosed between January 2010 and June 2016 in Accra, Ghana. Results: Of RT-TB patients, 161 (40.9%) were treated empirically (negative/absent smear, culture or Xpert), of whom 30.4% (49/161) had only extrapulmonary TB signs or symptoms. Mortality during treatment was 19.4%; 15-day mortality was 10.8%. In multivariable proportional hazards regression, living with HIV (aHR=2.69 [95 CI: 1.51, 4.80], p<0.01) and previous loss-to-follow up (aHR=8.27 (95 CI: 1.10, 62.25), p=0.04) were associated with mortality, while drug susceptibility testing (DST, aHR=0.36 (95 CI: 0.13, 1.01), p=0.052) was protective. Isoniazid resistance was observed in 40% (23/58 tested) and rifampin resistance in 19.1% (12/63 tested). Conclusion: High rates of extrapulmonary TB and smear/culture negative disease highlight the barriers to achieving DST-driven RT-TB regimens and the need for improved diagnostics. Our finding of poly-drug resistance in rifampin-susceptible cases supports access to comprehensive first line DST. Additionally, interventions to reduce mortality, especially in HIV co-infected RT-TB patients, are urgently needed.


Assuntos
Antituberculosos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose/tratamento farmacológico , Adulto , Antituberculosos/farmacologia , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Feminino , Gana , Infecções por HIV/epidemiologia , Humanos , Isoniazida/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Retratamento , Estudos Retrospectivos , Rifampina/farmacologia , Tuberculose/microbiologia , Tuberculose/mortalidade , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade
14.
Int J Nanomedicine ; 14: 4741-4754, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456635

RESUMO

Background: Ipomoea batatas (L.) Lam.(Ib) has high content of various beneficial nutrients which helps in improving and maintaining human health. It is well known as a functional food and also a valuable source of unique natural products. It contains various phenolic and flavonoid bioactive compounds. Methods: In this study, using the outer peel of two varieties of Ib : Korean red skin sweet potato and Korean pumpkin sweet potato, silver nanoparticles (AgNPs) were synthesized (termed Ib1-AgNps and Ib2-AgNps), respectively. Characterization of Ib1-AgNPs and Ib2-AgNPs was carried out through scanning electron microscopy, Fourier-transform infrared (FT-IR) spectroscopy, energy-dispersive X-ray analysis, X-ray powder diffraction and UV-Vis spectroscopy. Further, the bio-potential of the synthesized AgNPs was investigated by antidiabetic (α-glucosidase assay), antioxidant (free radical scavenging assays), antibacterial (disc diffusion method) and cytotoxicity assays (cell viability against HepG2 cells). Results: FT-IR spectroscopy revealed the contribution of bioactive compounds existing in Ib1 and Ib2 extracts, in the biosynthesis and equilibrium of the AgNPs. Although the Ib2-AgNPs had a higher atomic percentage of Ag in comparison with Ib1-AgNPs, in the antidiabetic assay, the inhibition percentage of α-glucosidase was higher for AgNPs of Ib1 than Ib2, at all three concentrations examined. From the cytotoxicity results, HepG2 cancer cells were more sensitive to the Ib1-AgNPs in comparison to the Ib2-AgNPs-treated HepG2 cells. The antioxidant prospective was higher in Ib2-AgNPs than Ib1-AgNPs. Moreover, the Ib2-AgNPs showed inhibitory action against all five tested pathogenic bacteria, producing an inhibition zone of 8.74-11.52 mm while Ib1-AgNPs had an inhibitory effect on four of them, with an 8.67-11.23 (mm) inhibition zone. Conclusions: Overall, the results concluded that the Ib2-AgNPs exhibited relatively higher functional activity than Ib1-AgNPs, which might be credited to the greater abundance of bioactive compounds existing in Ib2 extract that acted as reducing as well as capping agents in the synthesis of Ib2-AgNPs. Overall, the current study highlights a novel cost-effective and eco-friendly AgNPs synthesis using food waste peels with biocompatibility and could be potentially utilized in biomedical and pharmaceutical industries.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Ipomoea batatas/química , Nanopartículas Metálicas/química , Prata/farmacologia , Bactérias/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Hipoglicemiantes/farmacologia , Concentração Inibidora 50 , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , alfa-Glucosidases/metabolismo
15.
Pestic Biochem Physiol ; 159: 41-50, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400783

RESUMO

Emerging fungal phytodiseases are a food security threat and novel fungicides are in an urgent need. Herein, a series of isobutyrophenone derivatives were designed and synthesized. The derivatives exhibited excellent fungicidal activities against seven fungi. The structure-activity relationship (SAR) study indicated that the introduction of a bromo group at the position 3 or 5 of the phenyl ring, as well as esterification of the 4-hydroxy with a chloroacetyl group, could substantially increase the antifungal activity and spectrum of the compounds. Among all 23 compounds, 2-bromo-3-hydroxy-4-isobutyryl-6-methylphenyl 2-chloroacetate (12b) showed the highest fungicidal activity against all seven tested fungal pathogens with EC50 values ranging from 1.22 to 39.94 µg/mL and exhibited the most potent inhibition against class II fructose-1,6-bisphosphate aldolase with an IC50 of 3.63 µM. The lead compounds were proven to be safe to NIH3T3/293 T cells and silkworm larvae, and relatively stable under different harsh conditions. Detached fruit tests showed the practical potential of lead compounds for fruit (or plant) protection. Taken together, our results indicated that the isobutyrophenone derivatives could be further optimized and developed as advanced leads for new fungicides.


Assuntos
Antifúngicos/química , Antifúngicos/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Animais , Bombyx/metabolismo , Linhagem Celular , Frutose-Bifosfato Aldolase/genética , Humanos , Larva/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Células NIH 3T3 , Relação Estrutura-Atividade
16.
J Enzyme Inhib Med Chem ; 34(1): 1414-1425, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401901

RESUMO

The emergence of drug-resistant pathogenic bacteria is occurring due to the global overuse and misuse of ß-lactam antibiotics. Infections caused by some bacteria which secrete metallo-ß-lactamases (enzymes that inactivate ß-lactam antibiotics) are increasingly prevalent and have become a major worldwide threat to human health. These bacteria are resistant to ß-lactam antibiotics and MBL-inhibitor/ß-lactam antibiotic combination therapy can be a strategy to overcome this problem. So far, no clinically available inhibitors of metallo-ß-lactamases (MBLs) have been reported. In this study, L-benzyl tyrosine thiol carboxylic acid analogues (2a-2k) were synthesized after the study of computational simulation by adding of methyl, chloro, bromo and nitro groups to the benzyl ring for investigation of SAR analysis. Although the synthesized molecules 2a-k shows the potent inhibitory effects against metallo-ß-lactamase (IMP-1) with the range of Kic values of 1.04-4.77 µM, they are not as potent as the candidate inhibitor.


Assuntos
Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/farmacologia , Compostos de Sulfidrila/química , Tirosina/química , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Ácidos Carboxílicos/química , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/enzimologia , Relação Estrutura-Atividade , Inibidores de beta-Lactamases/química
17.
Phys Chem Chem Phys ; 21(32): 17821-17835, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31373340

RESUMO

The rise of New Delhi metallo-beta-lactamase-1 (NDM-1) producers is a major public health concern due to carbapenem resistance. Infections caused by carbapenem-resistant enterobacteria (CRE) are classified as a serious problem. To understand the structure and function of NDM-1, an amino acid replacement approach is considered as one of the methods to get structural insight. Therefore, we have generated novel mutations (N193A, S217A, G219A and T262A) near active sites and an omega-like loop to study the role of conserved residues of NDM-1. The minimum inhibitory concentrations (MICs) of ampicillin, imipenem, meropenem, cefotaxime, cefoxitin and ceftazidime for all mutants were found to be reduced 2 to 6 fold, compared to a wild type NDM-1 producing strain. The Km values increased while Kcat and Kcat/Km values were decreased compared to wild type. The affinity as well as the catalysis properties of these mutants were reduced considerably for imipenem, meropenem, cefotaxime, cefoxitin, and ceftazidimem compared to wild type, hence the catalytic efficiencies (Kcat/Km) of all mutant enzymes were reduced owing to the poor affinity of the enzyme. The IC50 values of these mutants with respect to each drug were reduced compared to wild type NDM-1. MD simulations and docking results from the mutant protein models, along with the wild type example, showed stable and consistent RMSD, RMSF and Rg behavior. The α-helix content values of all mutant proteins were reduced by 13%, 6%, 14% and 9% compared to NDM-1. Hence, this study revealed the impact role of active sites near residues on the enzyme catalytic activity of NDM-1.


Assuntos
Antibacterianos/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , beta-Lactamases/química , Antibacterianos/farmacologia , Biocatálise , Domínio Catalítico , Farmacorresistência Bacteriana , Cinética , Testes de Sensibilidade Microbiana , Mutagênese Sítio-Dirigida , Mutação , Ligação Proteica , Estrutura Secundária de Proteína , Termodinâmica , beta-Lactamases/genética , beta-Lactamases/metabolismo
18.
Pestic Biochem Physiol ; 158: 185-200, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31378356

RESUMO

The present work describes the antimicrobial action of 25 monoterpenes (six hydrocarbons, five ketones, two aldehydes, six alcohols and six acetate analogues) against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus and antifungal activity against Aspergillus flavus. The antibacterial activity was evaluated by broth microdilution technique as a minimum inhibitory concentration (MIC) and the antifungal activity was performed by mycelia radial growth technique as the effective concentration causing 50% inhibition of the mycelial growth (EC50). The results showed that thymol and α-terpineol were the most potent against E. coli (MIC = 45 and 55 mg/L, respectively) and S. aureus (MIC = 135 and 225 mg/L, respectively). The results also showed that thymol displayed the maximum antifungal action against A. flavus with EC50 20 mg/L. Furthermore, the antioxidant activity was determined using N,N-dimethyl-1,4-phenylenediamine (DMPD) and the results showed that geraniol were the most potent compound (IC50 = 19 mg/L). Molecular docking studies indicated that the compounds displayed different binding interactions with the amino acid residues at the catalytic sites of N5-carboxyaminoimidazole synthetase and oxysterol binding protein Osh4 enzymes. Non-covalent interactions including van der Waals, hydrogen bonding as well as hydrophobic were observed between the compounds and the enzymes. A significant relationship was found between the docking score and the biological activity of the tested monoterpenes compared to the ceftriaxone and carbendazim as standard bactericide and fungicide, respectively. In silico ADMET properties were also performed and displayed potential for the development of promising antimicrobial agents. For these reasons, these compounds may be considered as potential ecofriendly alternatives in food preservation to delay or prevent the microbial infection and prolong the shelf life of food products.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Monoterpenos/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/química , Cicloexenos/química , Cicloexenos/farmacologia , Escherichia coli/efeitos dos fármacos , Hidrocarbonetos/química , Hidrocarbonetos/farmacologia , Testes de Sensibilidade Microbiana , Monoterpenos/química , Monoterpenos/farmacologia , Staphylococcus aureus/efeitos dos fármacos
19.
Pestic Biochem Physiol ; 158: 25-31, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31378357

RESUMO

Sodium pheophorbide a (SPA) is a natural photosensitizer. To explore its antifungal activity and mechanism, we studied its inhibitory effects on spore germination and mycelial growth of Pestalotiopsis neglecta. We used sorbitol, 2-thiobarbituric acid (TBA) and electron microscopy to determine its effects on cell wall integrity, cell membrane lipid peroxidation and mycelial morphology. Finally, the effects of SPA on enzyme activity in mycelia were determined. The results showed that SPA effectively inhibited spore germination and mycelial growth of P. neglecta under light conditions (4000 lx, 24 h). Scanning electron microscopy (SEM) revealed that SPA treatment resulted in a roughened, twisted and knotted mycelial surface and abnormal mycelial growth. SPA influenced cell wall integrity, and the content of MDA, a cell membrane lipid peroxidation product was significantly increased (P < 0.05). SPA also significantly inhibited SOD, POD and PG activity, but enhanced PPO activity (P < 0.05). In conclusion, SPA may have potential to become a biological pesticide.


Assuntos
Antifúngicos/farmacologia , Clorofila/análogos & derivados , Micélio/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Clorofila/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Micélio/ultraestrutura
20.
Epidemiol Mikrobiol Imunol ; 68(2): 65-70, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31398978

RESUMO

BACKGROUNDS: Snails (Gastropoda) have a mechanism for the production of a significant amount of slime and substances contained therein they use to protect themselves against bacterial or fungal pathogens. These active substances are involved in both humoral and cellular immune responses of the gastropods. The antibacterial or antifungal effect of the humoral immune component of slime lies in cytotoxic and haemagglutination activity against potential microbial pathogens. The activity of antibacterial agents present in Achatina reticulata slime against bacterial strains of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa was tested. MATERIAL AND METHODS: A total of five samples of slime from laboratory reared Achatina reticulata were tested. To eliminate potential microbial contamination, slime samples were sterilized by UV radiation. To screen slime samples for antibacterial activity, the simple diffusion method on Mueller-Hinton agar was used. Samples diluted in guaiacol glycerol ether were used in the testing. RESULTS: The results show that the biologically active substances present in Achatina reticulata slime have an antimicrobial activity which is almost commensurate with that of the conventional antibiotics used to treat bacterial infections. The results of the determination of the antimicrobial effects of Achatina reticulata slime also highlighted viridation (partial hemolysis of erythrocytes after 24 hours of slime cultivation exposed to UV light for 60 minutes on Columbia blood agar. CONCLUSIONS: The results of the antimicrobial activity testing of selected Achatina reticulata slime samples show that the gastropod slime contains biologically active substances with a relatively significant antimicrobial activity.


Assuntos
Anti-Infecciosos , Bactérias , Gastrópodes , Animais , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Gastrópodes/microbiologia , Testes de Sensibilidade Microbiana , Muco/microbiologia
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